Analysis of Clinical Features, Diagnostic Tests, and Biomarkers in Patients With Suspected Creutzfeldt-Jakob Disease, 2014-2021
Authors: Dror Shir, Evelyn B. Lazar, Jonathan Graff-Radford, Allen J. Aksamit, Jeremy K. Cutsforth-Gregory, David T. Jones, Hugo Botha, Vijay K. Ramanan, Christian Prusinski, Amanda Porter, Gregory S. Day
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Detection of prion proteins in cerebrospinal fluid (CSF) using real-time quaking-induced conversion (RT-QuIC) assays has transformed the diagnostic approach to sporadic Creutzfeldt-Jakob disease (CJD), facilitating earlier and more complete recognition of affected patients. It is unclear how expanded recognition of affected patients may affect the diagnostic and prognostic relevance of clinical features and diagnostic tests historically associated with CJD. <h3>Objective</h3> To evaluate clinical features and diagnostic testing in patients presenting with CJD and determine the associations of these features with prognosis. <h3>Design, Setting, and Participants</h3> This cohort study incorporated data from electronic medical records of patients with CJD treated at Mayo Clinic Enterprise tertiary care centers in Rochester, Minnesota; Jacksonville, Florida; and Scottsdale, Arizona. Participants included patients with definite or probable CJD assessed from 2014 to 2021. Data were analyzed October 2021 to January 2022. <h3>Exposures</h3> Dominant presentation, clinical features, and diagnostic tests associated with CJD. <h3>Main Outcomes and Measures</h3> The outcomes of interest were the sensitivity and prognostic value of clinical features and accessible diagnostic tests at presentation with possible CJD. <h3>Results</h3> A total of 115 patients were identified, including 40 patients (35%) with definite CJD. Mean (SD) age at symptom onset was 64.8 (9.4) years, and 68 patients were women (59%). The sensitivity of clinical markers (myoclonus) and tests historically considered in patients with suspected CJD was poor (eg, stereotyped electroencephalography anomalies: 17 of 105 patients [16%]; elevated CSF protein 14-3-3 levels: 54 of 90 patients [60%]). By comparison, biomarkers with good diagnostic sensitivity at presentation included RT-QuIC (66 of 71 patients [93%]), CSF total tau (T-tau) level greater than 1149 pg/mL (81 of 92 patients [88%]), and characteristic signal anomalies on magnetic resonance imaging (88 of 115 patients [77%]). Multivariable linear regression confirmed shorter survival in patients with myoclonus (difference, −125.9 [95% CI, −236.3 to −15.5] days;<i>P</i> = .03), visual or cerebellar signs (difference, −180.2 [95% CI, −282.2 to −78.2] days;<i>P</i> &lt; .001), elevated CSF protein 14-3-3 levels (difference, −193 [95% CI, −304.9 to −82.9] days;<i>P</i> &lt; .001), and elevated T-tau level (difference for every 1000 pg/mL elevation, −9.1 [95% CI, −17.7 to −1.0] days;<i>P</i> = .04). <h3>Conclusions and Relevance</h3> These findings suggest that CSF RT-QuIC, elevated CSF T-tau level, and stereotyped magnetic resonance imaging anomalies were associated with the diagnosis of CJD, while other clinical findings (eg, myoclonus), stereotyped electroencephalography anomalies, and CSF protein 14-3-3 levels offered less diagnostic value. Visual or cerebellar features, myoclonus, and CSF 14-3-3 and T-tau levels may be associated with disease duration, justifying continued inclusion in the evaluation of patients suspected to have CJD.